Christine M. Gabardo

Prototyping of wrinkled nano-/microstructured electrodes for electrochemical DNA detection.

Biosensing platforms are ideal for addressing the diagnostic needs of resource-poor areas; however, the translation of such systems from the laboratory to the point-of-need has been a slow process. Rapid prototyping methods that enable an application-specific biosensor to be created in a matter of hours from design to fabrication would expedite the clinical and field testing of such systems. Here, we demonstrate a benchtop method based on craft cutting and polymer-induced wrinkling for creating multiplexed electrochemical DNA biosensors. This fabrication method allows multiscale wrinkled electrodes with features in the millimeter to nanometer length scales to be created in a matter of hours. These wrinkled electrodes display an enhanced surface area compared to planar electrodes and are shown to be structurally tunable by changing the film thickness. We demonstrate that structural tunability of these electrodes is translatable to functional tunability as the density of surface-immobilized probe molecules can be manipulated using wrinkled electrodes of different thicknesses. Furthermore, a simple proof-of-concept electrocatalytic DNA biosensor is demonstrated for distinguishing between complementary and noncomplementary oligonucleotides.

Rapid prototyping of all-solution-processed multi-lengthscale electrodes using polymer-induced thin film wrinkling

Three-dimensional electrodes that are controllable over multiple lengthscales are very important for use in bioanalytical systems that integrate solid-phase devices with solution-phase samples. Here we present a fabrication method based on all-solution-processing and thin film wrinkling using smart polymers that is ideal for rapid prototyping of tunable three-dimensional electrodes and is extendable to large volume manufacturing. Although all-solution-processing is an attractive alternative to vapor-based techniques for low-cost manufacturing of electrodes, it often results in films suffering from low conductivity and poor substrate adhesion. These limitations are addressed here by using a smart polymer to create a conformal layer of overlapping wrinkles on the substrate to shorten the current path and embed the conductor onto the polymer layer. The structural evolution of these wrinkled electrodes, deposited by electroless deposition onto a nanoparticle seed layer, is studied at varying deposition times to understand its effects on structural parameters such as porosity, wrinkle wavelength and height. Furthermore, the effect of structural parameters on functional properties such as electro-active surface area and surface-enhanced Raman scattering is investigated. It is found that wrinkling of electroless-deposited thin films can be used to reduce sheet resistance, increase surface area, and enhance the surface-enhanced Raman scattering signal.

Programmable Wrinkling of Self-Assembled Nanoparticle Films on Shape Memory Polymers.

Hierarchically structured materials, inspired by sophisticated structures found in nature, are finding increasing applications in a variety of fields. Here, we describe the fabrication of wrinkled gold nanoparticle films, which leverage the structural tunability of gold nanoparticles to program the wavelength and amplitude of gold wrinkles. We have carefully examined the structural evolution and tuning of these wrinkled surfaces through varying nanoparticle parameters (diameter, number of layers, density) and substrate parameters (number of axes constrained during wrinkling) through scanning electron microscopy and cross-sectional transmission electron microscopy. It is found that nanoparticle layers of sufficient density are required to obtain periodical wrinkled structures. It was also found that tuning the nanoparticle diameter and number of layers can be used to program the wrinkle wavelength and amplitude by changing the film thickness and mechanical properties. This dual degree of tunability, not previously seen with continuous films, allows us to develop one of the smallest wrinkles developed to date with tunability in the sub-100 nm regime. The effect of the induced structural tunability on the enhancement of the intensity of the 4-mercaptopyridine Raman spectra is also studied through the application of these devices as substrates for surface-enhanced Raman spectroscopy (SERS), where wrinkling proves to be an effective method for enhancing the SERS signal in cases where there is an inherently low density of gold nanoparticles.

An algorithm to discover gene signatures with predictive potential

BackgroundThe advent of global gene expression profiling has generated unprecedented insight into our molecular understanding of cancer, including breast cancer. For example, human breast cancer patients display significant diversity in terms of their survival, recurrence, metastasis as well as response to treatment. These patient outcomes can be predicted by the transcriptional programs of their individual breast tumors. Predictive gene signatures allow us to correctly classify human breast tumors into various risk groups as well as to more accurately target therapy to ensure more durable cancer treatment.ResultsHere we present a novel algorithm to generate gene signatures with predictive potential. The method first classifies the expression intensity for each gene as determined by global gene expression profiling as low, average or high. The matrix containing the classified data for each gene is then used to score the expression of each gene based its individual ability to predict the patient characteristic of interest. Finally, all examined genes are ranked based on their predictive ability and the most highly ranked genes are included in the master gene signature, which is then ready for use as a predictor. This method was used to accurately predict the survival outcomes in a cohort of human breast cancer patients.ConclusionsWe confirmed the capacity of our algorithm to generate gene signatures with bona fide predictive ability. The simplicity of our algorithm will enable biological researchers to quickly generate valuable gene signatures without specialized software or extensive bioinformatics training.

A New Wrinkle in Biosensors: Wrinkled electrodes could be a breakthrough for lab-on-a-chip devices.

POC DNA biosensors have the potential to revolutionize health care by enabling expedited, patient-centered, and accessible health management at a low cost. Developing such systems requires the integration of several devices into a single platform, using an iterative design, implementation, testing, and clinical validation process. As a result, rapid prototyping methods, with a potential for manufacturing scale-up, are of particular importance for translating biosensing systems from the research lab to the market. Three-dimensional electrodes with features optimized over multiple length-scales have advantages over planar electrodes for biosensing applications where solid-phase devices are interfaced with liquid-phase solutions. Wrinkling is a novel method for creating topographically structured surfaces controllable at the micro and nano scale. We have developed a new rapid-fabrication technique that combines wrinkling and xurography to create multiscale electrodes in a controllable manner with a design-to-device duration of a few hours. These electrodes display excellent physical, mechanical, electrical, and electrochemical properties compared to their nonwrinkled counterparts. We have shown that we can apply this fabrication process to manufacture cellular lysis, magnetic manipulation, and nucleic-acid biosensing devices, which are essential components of a POC biosensing system. We expect this rapid prototyping method to expedite the research and development phase of several devices that rely on patterned micro/nanostructured electrodes.